Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease Academic Article uri icon

Overview

MeSH Major

  • Epithelial Cells
  • Gastrointestinal Microbiome
  • Graft vs Host Disease
  • Intestines
  • Metabolome

abstract

  • The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity.

publication date

  • May 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4836986

Digital Object Identifier (DOI)

  • 10.1038/ni.3400

PubMed ID

  • 26998764

Additional Document Info

start page

  • 505

end page

  • 13

volume

  • 17

number

  • 5